Based on our studies defining the antiviral mechanisms of polyanionic polysaccharide compounds, we are now analyzing the role of proteoglycans in the HIV infectious process. Characterization of the proteoglycan content of both resting and activated peripheral blood lymphocyte and monocytes has revealed a complex array of heparan sulfates and chondroitin sulfates on the cell surface, which are upregulated and released by cell activation. Experimental enzyme modification of cell surface proteoglycans followed by assays for HIV infection and syncytia formation have found that proteoglycans provide binding sites for HIV on the cell surface, which depending on the cellular activation environment either interfere with or potentiate HIV infection and syncytia formation.